A Retrospective Study of the Efficacy and Safety of Naldemedine for Treatment of Opioid-Induced Constipation in Patients with Hepatobiliary Pancreatic Cancer.

Background and Objectives : Opioid analgesics, which are used for cancer-related pain management, cause opioid-induced constipation (OIC). Naldemedine, a peripheral opioid receptor antagonist, is an OIC-modifying agent, but no focused efficacy and safety analysis has been conducted for its use in hepatobiliary pancreatic cancers. We performed a multi-institutional study on the efficacy and safety of naldemedine in patients with hepatobiliary pancreatic cancer using opioids in clinical practice. Materials and Methods : We retrospectively evaluated patients with hepatobiliary pancreatic cancer (including liver, biliary tract, and pancreatic cancers) treated with opioids and naldemedine during hospitalization at ten institutions in Japan from June 2017 to August 2019. We assessed the frequency of bowel movements before and after the initiation of naldemedine therapy. Responders were defined as patients who defecated ≥3 times/week, with an increase from a baseline of ≥1 defecations/week over seven days after the initiation of naldemedine administration. Results : Thirty-four patients were observed for one week before and one week after starting naldemedine. The frequency of bowel movements increased by one over the baseline frequency or to at least thrice per week in 21 patients. The response rate was 61.7% (95% confidence interval: 45.4-78.0%). The median number of weekly bowel movements before and after naldemedine treatment was 2 (range: 0-9) and 6 (range: 1-17), respectively, in the overall population (n = 34); the increase in the number of bowel movements following naldemedine administration was statistically significant (Wilcoxon signed-rank test, p < 0.0001). Diarrhea was the predominant gastrointestinal symptom, and 10 (29.4%) patients experienced grade 1, grade 2, or grade 3 adverse events. The only other adverse event included fatigue in one patient; grade 2-4 adverse events were absent. Conclusions : Naldemedine is effective, and its use may be safe in clinical practice for patients with hepatobiliary pancreatic cancer receiving opioid analgesics.